This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Virtual Cell is a general modeling tool, freely available over the Internet, designed specifically for experimental biologists. The software permits the user to formulate complex biochemical reaction pathways including membrane transport and electrophysiology with a simple biology-oriented graphical user interface. To model specific pathways and networks in the Virtual Cell, molecular species are first added by name, and reactions entered using a simple reaction editor. Each reaction created in this way is then assigned to the appropriate compartment within the cell, building a complete pathway. The compartments can subsequently be mapped to either an approximation of well-mixed uniform regions (compartmental model), or to geometries constructed from analytical expressions, or derived directly from microscope images of the cell under study. For each specific interaction described in the model, the user chooses the appropriate kinetic formalism and inputs relevant parameter values . A system of mathematical equations representing the model is then automatically generated by the software. All these activities are completed on the user's computer, using a sophisticated Java-based user interface uploaded automatically at the beginning of the session, and the results of it are saved to the Virtual Cell Database (VCDB) on UCHC servers. Simulations based on the model and incorporating specific experimental conditions are then solved using a choice of available numerical methods, which use hardware and software resources (e.g. highperformance clusters of computers, specific solvers, libraries, and compilers) from our central facility. Results of simulations are saved to a high-capacity data storage facility and linked into the VCDB, and can be viewed and exported to a number of formats that can be loaded and further analyzed with available imaging or spreadsheet software.